PROJECT SUMMARY/ABSTRACT Neurodegenerative diseases including Alzheimer's (AD) and Parkinson's disease (PD) are distressing conditions for those affected and their loved ones, and represent a growing burden on public health funds. These diseases are becoming increasingly prevalent as the population ages. Neuropsychological decline is the hallmark of early AD, and is common in PD. Such symptoms are identified and tracked with neuropsychological tests, which are also important in testing new medications. Recent breakthroughs have led to further understanding of the underlying neurobiology of AD and PD, but how these new findings relate to neuropsychological testing is largely unknown. This project will inform our interpretation of neuropsychological testing in relation to novel neuroimaging and genetic biomarkers of AD and PD. In AD, we will we will study the brain at rest using functional magnetic resonance imaging (fMRI), and learn how the connectivity of the brain's networks relate to neuropsychological testing. We will also use a novel adaptation of a task traditionally used in rodent studies, the Morris Water Maze, and understand this in the context of connectivity at rest during fMRI. Other aspects of the project will involve both AD and PD: we will use a novel method to assess inflammation in the brain, and understand how regional inflammation relates to different types of cognitive impairment. We will also discover how genetic biomarkers of inflammation and AD risk relate to neuropsychology. By gaining better understanding of the correlations of neuropsychology and these novel biomarkers we will be able to inform interpretation of both sets of techniques. Neuropsychology is currently central to the monitoring of novel medications being tested in both diseases, and understanding the neurobiological processes underlying our findings will be central in contributing to the development of new medications. The studies outlined in this project proposal will generate preliminary data to answer further questions about the neuropsychology of these diseases. In combination with a detailed mentoring scheme, the studies proposed here and the experience gained if funded will result in the project leader being a competitive candidate for independent research funding.